US20020098097A1 - Magnetically-actuated micropump - Google Patents

Abstract

A microfluidic pump having a substrate with a pump chamber and at least one channel in communication with the pump chamber for transporting a substance into or out of the pump chamber. A flexible diaphragm overlies the pump chamber, and a magnetic member is attached to the diaphragm. A magnet, such as an electromagnet, is positioned to attract and repel the magnetic member, thereby actuating the diaphragm, and causing a substance to be drawn into or out of the channel. A uni-directional or bi-directional check valve can be positioned in the channel to prevent backflow into the pump chamber. A control system can be coupled to the pump to adjust actuation rate of the diaphragm.

Description

CROSS-REFERENCE TO RELATED APPLICATION
• This application is related to and incorporates by reference herein in its entirety the commonly owned and concurrently files patent application Attorney Docket Number M-9289 entitled “AUTOMATED MICROFABRICATION-BASED BIODETECTOR” by Angad Singh and Shahzi S. Iqbal.[0001]
BACKGROUND OF THE INVENTION
• 1. Field of the Invention[0002]
• This invention relates generally to micropumps. More specifically, this invention relates to a micropump that is magnetically actuated.[0003]
• 2. Description of the Related Art[0004]
• There are several applications that require pumps for transporting substances from one location to another. Some of these applications include medical implants, miniature scrubbing systems, chemical analysis of very small samples, and medical diagnosis. Pumps having nanometer-scale dimensions are required in some of these situations. Microfabrication techniques are well-known in the art, and are capable of producing very small scale components with moving parts. It is nonetheless desirable to provide a micropump that is capable of delivering the appropriate amount of a substance using a minimum number of moving parts to simplify fabrication.[0005]
SUMMARY OF THE INVENTION
• A pump (also called “microfluidic pump”) in accordance with the invention has a substrate with a chamber (also called “pump chamber”) and at least one channel in communication with the pump chamber for transporting a substance into or out of the pump chamber through one or more channels. A flexible diaphragm forms a wall of the pump chamber, and the pump operates when the diaphragm is flexed.[0006]
• In one embodiment, a magnetic member is attached to the diaphragm. A magnet, such as an electromagnet, is positioned to attract and repel the magnetic member, thereby actuating the diaphragm, and causing a substance to be drawn into or out of the pump chamber through the channel. Depending on the embodiment, a uni-directional or bi-directional check valve can be positioned in the channel to allow flow of the substance into the chamber or to prevent backflow into the pump chamber. Also depending on the embodiment, a control system can be coupled to the pump to sense the flow rate of the substance in the channel, and to adjust actuation rate of the diaphragm based on the flow rate. Moreover, as an option, a protective layer can be included to cover the top of the diaphragm. Another protective layer can be included to cover the bottom of the substrate.[0007]
• Depending on the implementation, the substrate and diaphragm can be fabricated with polymer materials that are injection molded, etched, or embossed with the components such as the chamber, channels, and valves.[0008]
• The present invention advantageously provides a micropump with a minimum number of moving parts to improve reliability and cost-effectiveness. The micropump is also decoupled from the actuating mechanism. The advantage of this feature is that the pump can be included in a disposable portion of a system, while the actuating mechanism is included on a non-disposable portion of the system and can be used to actuate other micropumps.[0009]
• The foregoing has outlined rather broadly the features and technical advantages of the present invention so that the detailed description of the invention that follows can be better understood.[0010]
BRIEF DESCRIPTION OF THE DRAWINGS
• FIG. 1 is a block diagram of components included in an embodiment of a bio-sensor system in accordance with the present invention.[0011]
• FIG. 1[0012]ais a block diagram of components included in an embodiment of a bio-sensor device in accordance with the present invention.
• FIGS. 1[0013]aa-1aware schematic diagrams of circuits included in a biosensor system in accordance with an embodiment of the present invention.
• FIG. 1[0014]bis a top view of components included in an embodiment of a bio-sensor device in accordance with the present invention.
• FIG. 1[0015]cis a side cross-section view of components included in an embodiment of a bio-sensor device in accordance with the present invention.
• FIG. 2 is a block diagram of components included in an embodiment of a microfluidic system for the bio-sensor in accordance with the present invention.[0016]
• FIG. 2[0017]ais a flowchart of protocols for detecting viruses, bacteria, and toxins using a bio-sensor system in accordance with the present invention.
• FIG. 3[0018]ais a side of view of a filtration/concentration assembly in accordance with the present invention.
• FIG. 3[0019]bis a side of view of a portion of the filtration/concentration assembly that is used to introduce a sample to a microfluidic system in accordance with the present invention.
• FIG. 3[0020]cis a side of view of the electro-magnetically actuated pump in accordance with the present invention.
• FIG. 3[0021]dis a top view of the electro-magnetically actuated pump and check valve in accordance with the present invention.
• FIG. 3[0022]eis a block diagram of a microfluidic pump coupled to a feedback and control system in accordance with the present invention.
• FIG. 3[0023]fis a block diagram of a piezoelectric pump coupled to a feedback and control system in accordance with the present invention.
• FIG. 3[0024]gis a diagram of a mixer in accordance with the present invention.
• FIG. 4 is a diagram of an information network in accordance with the present invention.[0025]
• The present invention may be better understood, and its numerous objects, features, and advantages made apparent to those skilled in the art by referencing the accompanying drawings. The use of the same reference symbols in different drawings indicates similar or identical items.[0026]
DETAILED DESCRIPTION
• Referring to FIG. 1,[0027]biosensor system100 is shown includingbio-sensor device102,microfluidic system104, andnetwork interface106 toworkstation108. In one embodiment,microfluidic system104 incorporates components that are required for performing chemical and/or biological processes on a sample of a substance to be analyzed.Microfluidic system104 can be inserted and removed frombiosensor device102.Biosensor device102 is a portable, hand-held unit that includes a user interface and display, an interface tomicrofluidic system104, and annetwork interface106 to one ormore workstations108 that allows a user atworkstation108 to access data collected usingbiosensor system100.Biosensor system100 can also be used as aworkstation108.
• Referring now to FIGS. 1 and 1[0028]a, a block diagram of one embodiment ofbiosensor device102 is shown in FIG.1a. Power supply110 provides operating power to various components onbiosensor device102 including digital signal (DSP) and input/output (I/O)processor112,driver circuits114,analog circuits116, adisplay118,valves120,thermistor122, thermo-electric cooler124, pump coils126, anddetection system128.Power supply110 can be one or more commercially available power supplies, such as an internal DC battery or a power regulator that interfaces to an external AC supply.Power supply110 is capable of providing one or more operating voltages at the levels required by the components ofbiosensor device102.Biosensor device102 can also be powered via a universal serial bus (USB)port130 with theworkstation108.
• In the embodiment shown in FIG. 1[0029]a, data processing functions are divided among DSP and input/output (I/O)processor112,driver circuits114, andanalog circuits116. It is important to note, however, that data processing functions can be distributed using additional or fewer processors than shown in FIG. 1a. FIGS. 1aathrough1ajare schematic diagrams showing examples of interface circuits betweenDSP131 and components in DSP and I/O processor112. FIG. 1abshows an example of an interface to programmable memory140 for storing DSP program instructions. FIG. 1acshows an example of an interface to Analog toDigital converter ADC148 which converts analog voltage level (e.g., temperature & fluorescence level) to a digital signal which can be used by the DSP. FIG. 1adshows an example of an interface to digital to analogsignal converter DAC146 which provides analog output voltage. FIG. 1aeshows an example of an interface tomemory142 for non-volatile memory storage. FIG. 1afshows an example of an interface to RS-232serial interface133. FIG. 1agshows an example of an interface to device indicators144. FIGS. 1ahand1ajshow examples of an interface to digital I/O150, which also interfaces with thedriver circuits114. FIG. 1aishows an example of an interface toUSB port130.
• FIG. 1[0030]akis an example of a schematic onanalog circuits board116 of a programmable amplifier that can be used to amplify the signal from the photo-multiplier-tube (PMT)184.
• FIGS. 1[0031]althrough1awshow examples of schematics fordriver circuits114. FIG. 1alshows an example of a programmable duty cycle generator for controlling the amount of power toTEC124. FIG. 1amshows an example of a DC to DC converter which conditions power supply voltage. For example, the circuit in FIG. 1amconverts a +12 volt (V) supply voltage to +5V, +12V and regulated +12V. FIG. 1anshows an example of an interface between DSP and I/O circuits112,analog circuits116, anddriver circuits114.
• FIGS. 1[0032]aoand1apshow examples of circuits which provide a set of digital control output signals for opening and closing, respectively,valves120. FIG. 1aqshows an example of a light emitting diode to indicate when power to the system100 (FIG. 1) is turned ON. FIG. 1arshows an example of a circuit for a piezoelectric buzzer for chip insert detection or user input detection. FIG. 1 shows an example of an interface connector for connectingDSP131 to other components in DSP and I/O processor112.
• [0033]Biosensor system100 also includes bridge circuits, examples of which are shown in schematics in FIGS. 1atthrough1aw. FIG. 1atis an example of circuit for controlling TEC124 (FIG. 1a). FIG. 1auis a bridge circuit used for controlling the current through the pump coil(s)126 (FIG. 1a). FIG. 1avis a laser diode driver circuit which maintains a constant light output from the laser182 (FIG. 1a) by regulating the current to the laser. FIG. 1awis an example of aconnector152 which can be used to interface themicrofluidic system104 tobiosensor device102.
• Examples of commercially available components which are suitable for use in the circuits shown in FIGS. 1[0034]aathrough1aware as follows: FIG. 1aa: DSP chip ADSP-2181, part # ADSP-2181KS-115 by Analog Devices, Norwood, Mass.; FIG. 1ab: EEP ROM (memory) chip, part # CAT28F512 by Catalyst Semiconductor, Sunnyvale, Calif.; FIG. 1ac: Analog-to-digital converter chip, part # AD7887 by Analog Devices, Norwood, Mass.; FIG. 1ad: Digital-to-analog converter chip, part # AD5322 by Analog Devices, Norwood, Mass.; FIG. 1ae: EEPROM (memory) chip, part # 24LC256 by Microchip Technology, Farmington Hills, Mich.; FIG. 1af: RS-232 chip, part #DS14C232 by Dallas Semiconductor, Dallas, Tex.; FIG. 1ag: demultiplexer chip, part # MC74HC138 by ON Semiconductor, Phoenix, Ariz.; FIG. 1ah: Digital output gates and flip-flop chips, part #s MC74HC32 and MC74HC574 by ON Semiconductor, Phoenix, Ariz.; FIG. 1ai: USB interface chip, part # PDIUSBD12D by Phillip Semiconductor, Sunnyvale, Calif., and gate 74HC08 by ON Semiconductor, Phoenix, Ariz.; FIG. 1aj: flip-flop and gate chips, part #s MC74HC573 and MC74HC32 respectively by ON Semiconductor, Phoenix, Ariz.; FIG. 1ak: Programmable gain amplifier chips, part # PGA103 by Burr-Brown Corporation/Texas Instruments, Dallas, Tex., and operational amplifier OP27 by Analog Devices, Norwood, Mass.; FIG. 1al: Shift registers, part #74HC165 by ON Semiconductor, inverters, part #74HC14 and #74HC04 by ON Semiconductor, Phoenix, Ariz.; FIG. 1am: DC-DC converter chips COSEL_ZU, part # ZUS 1R5 1205 by Cosel USA, San Jose, Calif. and AA01D_DUAL, part # AA01D-012L-120D by Astec America, Carlsbad, Calif.; FIG. 1ao: Flip-flop, part # 74HC574 by ON Semiconductor, and gate 74HC32 also by ON Semiconductor, Phoenix, Ariz.; FIG. 1ap: Same as FIG. 1ao; FIG. 1at: Gates, part #74HC14 and part #74HC08 by ON Semiconductor, Phoenix, Ariz.; FIG. 1au: Same as FIG. 1at; FIG. 1av: inverters, part # 74HC14 by ON Semiconductor, and laser diode driver, part # iC-WJ by iC-Haus, Bodenheim, Germany.
• [0035]Microfluidic system104 includes microfabricated components for performing biological and chemical analysis. Such components can include, for example, filters, valves, pumps, mixers, channels, reservoirs, and actuators.Detection system128 is used to detect target molecules that are the subject of the assay(s) that are performed usingmicrofluidic system104. Onesuch detection system128 includes an infrared (IR) laser and detector which is used to illuminate and detect IR dye, respectively, known as deoxynucleotide triphosphates (dNTPs) that can be used in the assays performed bymicrofluidic system104. Other suitable detection systems can be implemented withmicrofluidic system104 in addition to, or instead of, an IR detection system.Detection system128, andmicrofluidic system104 are discussed more fully hereinbelow.
• In one embodiment,[0036]microfluidic system104 is disposable and can be inserted and removed frombiosensor device102 as required. This allows a newmicrofluidic system104 to be used for each new sample to be analyzed, thereby reducing the risk of contamination from previous samples.
• DSP and I/[0037]O processor112 includes adigital signal processor131 for digital signal processing along withmain program instructions132 that control execution of components included inprocessor112.Main program instructions132 also control communication with components external toprocessor112. In one embodiment,digital signal processor131 is a single-microfluidic system104 microcomputer optimized for digital signal processing (DSP) and other high speed numeric processing applications.Digital signal processor131 includes one or more serial data interfaces such as RS2-32interface133 and Universal Serial Bus (USB)interface130. A peripheral device interconnect USB134 shown, for example, as PDIUSBD12, allows conventional peripherals to be upgraded to USB devices and take advantage of the “hot plug and play” capability of the USB, as known in the art. The USB134 interfaces with most device class specifications such as imaging, mass storage, communications, printing and human interface devices. USB134 communicates withdigital signal processor131 using a high-speed, general-purposeparallel interface138. Other data interfaces can be included in addition to or instead ofinterfaces133 and134.
• [0038]Digital signal processor131 also interfaces with other devices well-known in the art, including program anddata memory140,142 for storing data and executing program instructions, device indicators144, such as switches and lights, digital to analog (DAC) and analog to digital (ADC)converters146,148, and digital I/O controller150.Digital signal processor131 can also include a programmable timer and interrupt capabilities, as known in the art. Power-down circuitry can also be provided to conserve power when operatingbiosensor device102. One example of a microprocessor currently available that is suitable for use with present invention is model number ADSP-2181 manufactured by Analog Devices, Inc. in Norwood, Mass.
• [0039]Driver circuits114 interface withmicrofluidics system104 viaconnector152 to communicate withvalves120,thermistor122, thermoelectric cooler (TEC)124, pumps126.Driver circuits114 also interface withdetection system128 inbiosensor device102.Connector152 can be one of several connectors that are well known in the art and commercially available. One such connector is part # FH12-50S-0.5SH by Hirose Electric Co. Ltd.
• Driver circuits include[0040]thermistor driver153 and TEC driver154 which generate signals to control the operation ofthermistor122 andTEC124, respectively.Pump driver156 includes logic to determine voltage signals required to operate pumps126. The signals input tomicrofluidic system104 to drivepumps126 can be based on information provided by flow sensors157microfluidic system104, wherein the sensors157 indicate the amount or rate of flow of a substance through one or more pumps126.Laser driver158 generates signals to control operation of a laser indetection system128. Such a laser is used for fluorescence detection, as further discussed hereinbelow.
• [0041]Insert detector162 receives information frommicrofluidic system104 that indicates whenmicrofluidic system104 is inserted inbiosensor device102. Whenmicrofluidic system104 is inserted inbiosensor device102,processors112,114, and116 use the signal to begin operating other components inbiosensor device102.
• [0042]Valve driver164 sends signals to open andclose valves120microfluidic system104. A variety of valve and pump configurations can be implemented inmicrofluidic system104, depending on the processes to be performed. The processes typically occur in a particular sequence, and can also be timed. Thus,valve driver164 includes instructions for opening and closing each valve inmicrofluidic system104 for respective processes and reactions.Valve driver164,pump coil driver156,thermistor driver153, TEC driver154, andlaser driver158, can also share information to determine which functions to perform at the appropriate time.
• User interface (UI)[0043]module168 provides information and/or options to a user that is presented ondisplay118 and via device indicators144.UI module168 also receives input from one or more of a variety of known user input devices such as a keyboard, mouse, light pen, audio commands, or other data input device known in the art. It is important to note that a variety of suitable user input devices and displays, including audio, visual, and tactile input/output devices, are known in the art and can be incorporated with the present invention. The foregoing examples are not intended to limit the present invention to any particular input or display device, or combination of devices.
• [0044]Detection system128 generates data signals representing the substances detectedmicrofluidic system104, and the data signals are input toanalog circuits module116.Analog circuits module116 includes appropriate signal conditioning components174, as required, such as a sample and hold circuit, filter(s), and/or an amplifier(s). The output fromanalog circuits module116 is input to an analog to digital (A/D)converter148 in DSP and I/O processor112 for conversion from analog to digital form. This digital data can be further processed in DSP and I/O processor112, and the results output to display118 and/ornetwork interface106.
• A variety of processes are required to perform different biological and chemical assays. For example, detecting a particular biological or chemical agent in a sample can include distilling and purifying a sample, heating the sample, mixing the sample with various reactants, and filtering the treated sample to isolate the target agent.[0045]Biosensor device102 provides signals to actuate valves, pumps, and mixers to control the flow and mixing of the sample and various reactants to and from reservoirs inmicrofluidic system104.Biosensor device102 also provides control signals tothermistor driver153 and TEC driver154, which in turn provide signals to control operation ofthermistor122 andTEC124, respectively, during processes such as DNA/protein denaturation, single strand DNA annealing, and primer extension.Biosensor system102 can be programmed to perform a variety of assays that are performed automatically, or when selected by a user throughUI module168.
• DSP and I/[0046]O processor112,driver circuits114, andanalog circuits116 inbiosensor device102 can be implemented using a combination of hardware circuits, software, and firmware, as known in the art.
• One application of[0047]biosensor device102 is automating PCR analysis. Nano-scale devices for automating PCR and post-PCR analysis are available in the prior art, however, sample preparation including DNA/RNA isolation, and detection by PCR are still carried out manually as two different processes. Therefore, to fully exploit the potential of PCR-based detection,biosensor device102 advantageously integrates sample preparation, target amplification, and fluorescence detection into a single, portable, cost-effective device.Biosensor device102 can also be used for biological and chemical analysis processes in addition to, or instead of, PCR-based analysis.
• Referring now to FIGS. 1, 1[0048]a,1b, and1c, FIGS. 1band1cshow a top view and side cross-sectional view of components ofbiosensor system100 withmicrofluidics system104 inserted into thebiosensor device102.Electronic circuit cards180 control the operation of the optics inbiosensor system100, includinglaser diode source182 and photo-multiplier tube (PMT)184. In an alternate implementation, any other light source, such as a blue LED, can be used instead of, or in addition to,laser diode source182. Photodiode(s), or any other photo or electrical signal detection system, can be used, instead of, or in addition to,photomultiplier tube184 for fluorescence detection and/or measurement.Electronic circuit cards180 also include DSP and I/O processor112,driver circuits114, andanalog circuits116.
• There are a variety of[0049]different detection systems106 that can be implemented inbiosensor device102. Onesuch detection system128 that can be implemented inbiosensor100 is shown in FIGS. 1band1c.Detection system128 includes optical components such asmirrors185,186,diachroic filter188, andobjective lenses190,192. Incident light beams (excitation) fromlaser diode182 pass through adiachroic filter188 and are directed at a specific wavelength via amirror185 and anobjective lens190 in respective order, to the detection area on themicrofluidic system104. Reflected (emitted) light beams from the detection area on themicrofluidic system104 are directed via theobjective lens190,mirror185,diachroic filter188 andmirror186 at a specific wavelength, in respective order, to thedetector184, i.e., photomultiplier tube/photodiode. Emitted fluorescence (reflected light) is sensed by thedetector184, i.e., photomultiplier tube/photodiode.Detector184 generates data signals representing the emitted (reflected) light and the data signals are input to analog circuits116 (FIG. 1) for signal conditioning and conversion from analog to digital signals.
• [0050]Microfluidic system104 is inserted intobiosensor device102 and is guided to the appropriate position by one or more guide members194 which slides themicrofluidic system104 into position to connectelectrical connector152. Following insertion ofmicrofluidic system104, loading lever196 is released to allow spring member198 to placeTEC124 in contact withmicrofluidic system104. Additionally, electromagnetic pump coils199 are positioned adjacent to the top side of themicrofluidic system104. One or more of these coils199 can also be positioned on adjacent other sides ofmicrofluidic system104 to actuate pump(s)126.
• Referring now to FIG. 2, an embodiment of[0051]microfluidic system104 is shown including a plurality of pumps, valves, filters, mixers, reservoirs, and channels as described below.Connector152 is also shown inmicrofluidic system104, however the connections between theconnector152 and other components onmicrofluidic system104 are not shown for simplicity. The connections betweenconnector152 and the other components are used to communicate signals such as drive signals and detection signals.
• Note that the components shown and their placement with respect to one another in FIG. 2 depends on the particular processes to be performed using[0052]biosensor device102. Notably, the number of components and their position with respect to one another, can vary from the configuration shown in FIG. 2. Other types of components can be included in addition to those shown in FIG. 2.Microfluidic system104 can be configured with enough components to perform one or more protocols concurrently, or at different times with respect to one another. Further, some applications may not require the use of all the components in a given configuration. For example, a particular configuration ofmicrofluidic system104 can be used for more than one type of process. In this situation, one or more of the reservoirs may be used in some of the processes, but not in others due to different steps being required to prepare and process the sample. Additionally, the components, operate independently of one another, and can be controlled by an external or an embedded control system.
• Components can be included in[0053]microfluidic systems104 to perform processes to detect genes, toxins, viruses, bacteria, and vegetative cells.Microfluidic system104 is intended to include most, if not all, of the components required to perform the process from start to finish, and thus minimal user handling of the sample and intervention is required.Microfluidic system104 is also designed to be low-cost and hence disposable. These features advantageously lower the risk of contaminating the sample during testing. Further,microfluidic system104 yields highly reproducible results while requiring a relatively small sample size. For example, a 2.25 square inch disposablemicrofluidic system104 can accommodate a sample volume of 500-1000 microliters (before concentration) and a concentrated sample volume of 10 microliters.
• In some situations, a sample can contain a low concentration of molecules to be detected. In some embodiments, the dimensions of[0054]microfluidic system104 can range from one to two inches in length and height, and be less than one millimeter in thickness. Due to the small size ofmicrofluidic system104, the sample may need to be filtered and concentrated prior to performing the extraction and detection processes.
• Referring to FIG. 2, a sample containing varying amounts of targets, i.e., cells, virions, or toxins, can be loaded in[0055]sample entry port202 and subjected to a respective sample preparation procedure, such as concentration. This is accomplished by inputting the sample into filter204 to remove impurities that are larger in size than the target cells, viruses, or concentrates in the sample.
• FIG. 2[0056]ashows a flowchart of examples of protocols that may be implemented on microfluidic system204 (FIG. 2), includingbacteria protocol260 for isolating and purifying DNA from bacterial cells,virus protocol262 for isolating and purifying RNA from animal viruses, andtoxin protocol264 for isolating and purifying toxins.Protocols260,262, and264 are representative of the types of assays that can be performed on an appropriately configuredmicrofluidic system104.
• Referring to FIGS. 2 and 2[0057]a, once the sample is introduced tomicrofluidic system104, DNA/RNA purification that is used inprotocols260 and262 can be achieved as described in the following steps:
• 1. The sample is transferred to[0058]chamber208 by actuatingpump206, which can be a push button pump or an electronically actuated pump.
• 2. The sample is mixed/resuspended in lysozyme solution from[0059]reservoir210, which is transferred tomixer208 via actuation ofpump212.
• 3. A chamber in[0060]mixer208 is heated to 95 degrees centigrade for a period of time, for example, 2 minutes.
• 4. Protease (e.g. Proteinase K) in[0061]reservoir214 is pumped intomixer208 viapump215.
• 5. The lysed sample is pumped through[0062]microfilter216 intomixer220 viapump218. In one implementation,microfilter216 is a one to two micrometer filter. In other implementations, the size ofmicrofilter216 is selected based on the size of the target molecule.
• 6. A DNA wash solution (for example, Ethanol and salts buffer) is transferred from[0063]reservoir224 tomixer220 viapump228.
• 7. The sample+DNA wash solution from[0064]mixer220 is pumped to the wash discardreservoir232 viapump234 through amicrofilter230 or a nucleic acid binding agent such as glass milk.
• 8.[0065]Steps 6 and 7 can be repeated to concentrate DNA/RNA at themicrofilter230 or nucleic acid binding agent, and to discard proteins as well as other contaminants.
• 9. Aqueous solution from[0066]reservoir222 is pumped in the reverse direction through themicrofilter230 to the DNA/RNA collection chamber238 for PCR. At this point, the DNA/RNA is dissolved in the aqueous solution and is no longer bound tomicrofilter230.Collection chamber238 can either contain magnetic micro-beads or a polynucleotide array with assay-specific primers.
• For toxins or antigens (protein)[0067]protocol264 includes the following processes:
• 1. The sample is transferred to[0068]mixer208 by actuatingpump206, which can be a push button pump or an electronically actuated pump.
• 3. The toxin sample is mixed/resuspended in lysozyme solution from a reservoir such as[0069]210, which is transferred tochamber208 via actuation ofpump212.
• 4. Protease inhibitor from a reservoir such as[0070]214 is pumped into thelysis chamber208 viapump215.
• 5. The sample is pumped through[0071]microfilter216 intomixer220 viapump218.
• 6. A basic pH wash solution (for example, 0.1M Na[0072]₂CO₃buffer, pH=9.0) is transferred fromreservoir224 tomixer220 viapump228.
• 7. The sample+wash solution from[0073]mixer220 is pumped to the wash discardreservoir232 viapump234 through acationic microfilter230 or a protein binding agent such as cationic beads.
• 8.[0074]Steps 6 and 7 can be repeated to concentrate the toxin (protein) at themicrofilter230 or protein binding agent, and to discard nucleic acid as well as other contaminants and cell debris.
• 9. Neutral pH buffer solution (such as PBS pH=7.4 containing 1M NaCl), from[0075]reservoir222 is pumped through thecationic microfilter230 to theprotein collection chamber238 for immuno-PCR. At this point, the protein is dissolved in the neutral buffer and is no longer bound to themicrofilter230 or the protein binding agent. In the collection chamber the toxin is mixed with the respective antibodies conjugated with specific primers and allowed to bind at 37 degrees centigrade for a period of time, such as 5 minutes. The treated sample is transferred from thechamber208 to the collection chamber238 (PCR area) where a target bound to an antibody is captured for PCR-based signal amplification reaction and waste is discarded inreservoir232. Thecollection chamber238 can either contain magnetic micro-beads or a polynucleotide array with millions of assay-specific primers anchored to the surface.
• In one embodiment, millions of copies of the primers can be anchored on magnetic beads, such as those available from Bangs Laboratories, Inc. in Fishers, Ind. The target can be detected using known conjugating methods, such as streptavidin-biotin capture methods. Additionally, for high throughput amplification, an identical set of primers can also be supplied free in solution along with PCR reagents.[0076]
• After the target is extracted, purified, and captured in the[0077]collection chamber238, the target is denatured at 95 degrees centigrade, and allowed to anneal (hybridize) at 65° centigrade with the primers anchored to an array or magnetic microbeads. In this step, the two strands of DNA are separated and respective anchored primers, as well as primers free in solution (supplied as reagent), bind to the complimentary target sequences.
• Following hybridization, enzyme DNA polymerase, such as Taq DNA polymerase or rTth polymerase provided by, for example, PE Applied Biosystems in Foster City, Calif., elongates or synthesizes new complimentary strands in 5′→3′ incorporating labeled, i.e., fluorogenic dNTPs, at 72° C. In subsequent cycles of denaturation, annealing and elongation, newly synthesized strands (amplicons) serve as templates for exponential amplification of the target sequence. 3′ extension of the primers anchored to the surface leads to synthesis of fluorophore labeled target sequences covalently bound to the surface. Fluorophore labeling is accomplished by incorporation of fluorophore-dNTPs such as Cy5 dye-dCTP/dUTP. After removing free dNTPs and other reagents by washing, fluorescence is measured by detection system[0078]128 (FIG. 1).
• [0079]Microfluidic system104 can be configured and adapted to any of the nucleic acid-based assays, i.e., target amplification and hybridization-based signal amplification methods, as discussed in an article entitled “A Review of Molecular Recognition Technologies for Detection of Biological Threat Agents” by Iqbal, S. S., Michael, M. W., Bruno, J. G., Bronk, B. V., Batt, C. A., Chambers, J. P., Review article (2000). Biosensors and Bioelectronics.
• A microfilter that is suitable for use as filter[0080]204 can be fabricated by etching pillars that are spaced as closely as 1 micrometer apart in the substrate that is used as the base formicrofluidic system104. One or more of a variety of suitable materials can be used for the substrate, such as silicon and/or plastic. The pillars can be created by etching a material such as silicon, or by other processes that depend on the material being used, such as injection molding with plastic materials. The filter pillars can be fabricated along with the pump chambers, valves, and mixers. To create filters with smaller pore sizes, the pillars can be coated with a suitable material. For example, silicon pillars can be coated with a conformal material such as low-pressure-chemical-vapor-deposition (LPCVD) polysilicon, which is a standard material that is well-known in microfabrication art.
• FIG. 3[0081]ashows filtration/concentration assembly300 than can be used instead of, or in addition to, filter204.Assembly300 includes aloading chamber302, a receivingchamber304, and aplunger306. Loading chamber includes afunnel portion308 that mates with anotherfunnel portion310 on receivingchamber304 as shown in FIG. 3a. Onceloading chamber302 and receivingchamber304 are mated, the sample to be concentrated and filtered is introduced inloading chamber302.Plunger306 can be inserted in receivingchamber304 and pushed downward to force the sample throughfilter312.
• [0082]Filter312 is an appropriately sized microfilter, depending on the size of the molecule to be detected. A molecular weight cut off filter or a negatively charged fiber glass filter such as those commercially available from Memtec Limited, Timonium, Md., can be used.
• As the sample is pushed through[0083]filter312, the analytes of interest are retained and concentrated onfilter312 while the excess solution passes throughfilter312. Receivingchamber304 is open at the end to allow the excess solution to flow out.
• Once the runoff of the excess solution is completed,[0084]assembly300 is disassembled, receivingchamber304 is inverted and a volume of assay reagent is loaded in receivingchamber304. The volume of assay reagent can be as low as 5 to 25 microliters, depending on the size ofport202 in themicrofluidic system104.Plunger306 is inserted in the top of receivingchamber304, and funnelportion310 is inserted in port202 (FIG. 2) inmicrofluidic system104, as shown in FIG. 3b.Plunger306 is pushed downward to force the assay reagent thoughfilter312. Analytes previously concentrated onfilter312 are dissolved in the assay reagent and transferred intomicrofluidic system104 throughport202.
• Any suitable, commercially available thermal cycling device, such as a thermo-electric cooler (TEC)[0085]112 (FIG. 1) can be used to heat and cool the sample as described in the steps above. Size and power output of the TEC depends on the application. OptoTEC and ThermaTEC series TEC's by MELCOR Corporation in New Jersey are suitable for use in such in systems. Alternatively, resistive heaters microfabricated on themicrofluidic system104 can be used for heating while theTEC124 can be used for cooling.
• [0086]TEC124 is positioned on or near microfluidic system104 (FIG. 1) in close enough proximity to the chambers to effectively heat or cool the fluid(s). A silver-filled heat resistant adhesive with high thermal conductivity can be used to attachTEC124 to promote heat transfer. Alternatively,TEC124 can be included inbiosensor device102 such that it is aligned and spring-loaded to rest in a position to heat or cool the contents of the desired chambersmicrofluidic system104 when it is inserted intobiosensor device102.
• Temperature feedback for closed-loop control is provided by a thermocouple which is co-located with the[0087]TEC124. Thermocouples are a commercially available from numerous companies, for example, Newark Electronics Corporation in Chicago, Ill. and WakeField Engineering, Inc. in Beverly, Mass. Temperature feedback can also be provided by microfabricated temperature sensors that are built in tomicrofluidic system104.
• In one embodiment,[0088]microfluidic system104 has a planar design, i.e., all components can be fabricated in one step, which eliminates the need for stacking multiple layers and simplifies fabrication. Reservoirs can be sized according to the amount of substance to be stored in them. Reservoirs, mixers, and pumps can include access holes for loading sample(s) and reagents. The sample(s) and reagents can be introduced using a syringe and the holes can be sealed by laminating a film of a hydrophobic porous material, such as GORE-TEX® by W. L. Gore and Associates, Inc., which will act as a vent for trapped gases.
• A variety of materials and fabrication techniques can be used for monolithic fabrication of the pumps and other components of the planar system. In one embodiment, the system can etched out in a silicon substrate using a deep anisotropic silicon etching process known as ICP Multiplex System by Surface Technology Systems in the United Kingdom. A flexible glass cover can then be bonded to cover the channels and also form the diaphragm for the pumps. The flexible cover can also include electrical interconnects for various components in the substrate, and can be transparent to allow optical detection or viewing under a microscope.[0089]
• In another embodiment, the system can be embossed into a polymer substrate using an embossing tool manufactured by companies such as Jenoptik Microtechnic GmBH in Germany. In this case, a mold or negative replica of the system is first etched into silicon to form an embossing tool. The tool is then embossed into the polymer substrate at an appropriate softening temperature and then retracted. The tool can be reused to create more replicas reducing the cost per piece. Access holes can be drilled into the embossed polymer substrate. Another thin sheet of polymer can be chemically bonded to cover the channels.[0090]
• FIGS. 3[0091]cand3dshow a cross-sectional side view and a top view, respectively, of apump320 that is suitable for use in microfluidic system104 (FIG. 1).Pump320 includesdiaphragm338 that causes alternating volumetric changes in apump chamber340 when deflected. Whenpump chamber340 contains liquids or gases, they are transferred by the pumping action into another chamber or reservoir (not shown) viachannels342,344 insubstrate346. Checkvalves348,350 are located inchannels342,344, respectively, to control the flow of fluid into and out ofchamber340. Thediaphragm338 is actuated electro-magnetically withmagnetic member352 being controlled bymagnetic core354 and alternating current insolenoid356.
• Techniques known in the art, such as silicon etching, plastic injection molding, and hot embossing can also be used to fabricate[0092]microfluidic system104. A combination of fabrication methods well-known in the art can be used to fabricateflow channels342,344,pump chamber340, andcheck valves348,350 insubstrate346.
• In one embodiment, the top side of[0093]microfluidic system104 includeschannels342,344, and pumpchamber340. The top and bottom sides can includeaccess holes357,367 for loading reagents and other substances intochamber340, as required. The sample(s) and reagents can be introduced using a syringe and then accessholes357,367 are sealed by chemically bondinglayers360,362 to the top and/or bottom sides, respective.
• [0094]Microfluidic system104 can also be fabricated out of one or more layers of molded or embossed polymers. In one embodiment, channels, reservoirs, pump chambers, and check valves are embossed insubstrate346. A flexible layer is chemically bonded to the top ofsubstrate346, to formdiaphragm338 and seal the channels, reservoirs, and access holes on the top side.Magnetic members352 forpumps320 are positioned on top of the second layer. A topprotective layer360 and/or a bottomprotective layer362 can be included to seal and protect the top and bottom ofsubstrate346, as shown in FIG. 3c. The topprotective layer360 is flexible to allow movement ofdiaphragm352 during actuation.
• [0095]Diaphragm338 is attached to the top ofsubstrate346 and is made out of a thin sheet of flexible material such as plastic, glass, silicon, elastomer, or any other suitable, flexible material. The flexibility or stiffness required ofdiaphragm338 depends on the desired deflection of the diaphragm. Typically the stiffness is selected to achieve a total upward and downward deflection of approximately five to fifteen microns. Any suitable attachment mechanism, such as chemical bonding, can be used to attachdiaphragm338 tosubstrate346. The bonding technique utilized should be capable of maintaining the seal while thepump320 is operating.
• [0096]Magnetic member352 is made out of magnetic material which is attracted and repelled by a magnetic force frommagnetic core354.Magnetic member352 can be adhesively bonded todiaphragm338, or electroplated onto thediaphragm338 during manufacturing.Substrate346 can be made of plastic, silicon, or other suitable material that is capable of substantially retaining the shape ofpump chamber340 during operation.
• An electrically conductive wire is coiled around[0097]magnetic core354 to formsolenoid356. When an electric current passes throughsolenoid356, a magnetic field is created inmagnetic core354. The polarity of the current can be alternated to change the direction of force of the magnetic field, thus alternately repelling and attractingmagnetic member352. The repelling and attracting forces causediaphragm338 to move, changing the volume ofchamber340. An increase in volume draws fluid or gas intochamber340 viachannel342, and a decrease in volume forces the fluid or gas intochannel344. Applying a periodic excitation voltage tosolenoid356, such as provided bycurrent source364, causes diaphragm338 to oscillate, producing a pumping action. The flow rate is thus directly controlled by the frequency of the alternating current tosolenoid356.
• Note that the current through[0098]solenoid356 can have a positive or negative sign that produces a magnetic field inmagnetic core354. One end of themagnetic core354 becomes positively charged, and the other end becomes negatively charged. When the sign of the current throughsolenoid356 is reversed, the charge at the ends ofmagnetic core354 also reverse. When the current is shut off,magnetic core354 loses its magnetism. Further,magnetic member352 has a positively charged end, and a negatively charged end.Magnetic member352 is attracted tomagnetic core354 when the ends closest to each other are oppositely charged. Similarly,magnetic member352 is repelled bymagnetic core354 when the ends closest to each other have the same charge. The strength of the attraction or repulsion depends on the number of windings insolenoid356, and the strength of the electric current.
• [0099]Check valve348 controls the inflow of fluid or gas intochamber340, andcheck valve350 controls flow out ofchamber340.Check valve348 allows fluid to flow intochamber340 when the volume ofchamber340 is increased, and prevents backflow of the fluid or gas when the volume ofchamber340 is decreased. Flow throughchannel344 is controlled bycheck valve350, which allows flow intochannel344 when the volume ofchamber340 is decreased, and prevents backflow fromchannel344 when the volume ofchamber340 is increased.
• [0100]Pump337 is well-suited for use with a variety of devices, in addition tomicrofluidic system104, because the components associated withactuating pump337, namely,magnetic member352,magnetic core354, andcoil356, can be fabricated to a wide range of dimensions, including micro-scale dimensions. Flow rates can be adjusted by varying the frequency and amplitude of the alternating current throughsolenoid356. Additionally, an electronic, microprocessor-basedcontrol system366, as known in the art and shown in FIG. 3e, can be implemented to receive sensor input fromflow sensors368 that measure the flow into and/or out ofpump337. For example, a Digital Signal Processor such as model number ADSP-2181 by Analog Devices, Inc. of Norwood, Mass., can be used as the controller. Logic associated withcontrol system366 compares the actual flow rate to the desired flow rate, and provides a drive signal tocurrent source364 to adjust the frequency and amplitude of thecurrent source364 accordingly to achieve the desired flow rate frompump337.
• Referring again to FIGS. 3[0101]cand3d,magnetic member352 is located ondiaphragm338.Magnetic core354 is positioned close enough for its magnetic field to actuatediaphragm338.Magnetic core354 withsolenoid356 can be positioned abovemagnetic member352 or belowchamber340, depending on the strength of the magnetic field developed by the magnetic core. Instead of a single electromagnet, two magnets placed on opposite sides of themagnetic member352 can also be used in a push-pull configuration to maximize deflection. Further,magnetic core354,solenoid356, andcurrent source364 can be built into astructure surrounding substrate346,diaphragm338, andmagnetic member352.
• Other types of devices for creating magnetic fields for actuating the[0102]magnetic member352 can also be utilized with the present invention, instead of, or in addition to an electromagnet. For example, permanent magnets with opposing charges can be mounted on a structure that moves toward and away from themagnetic member352 at a periodic, variable rate, thereby actuatingdiaphragm338. The magnet having a like charge to themagnetic member352 would be used to repel themagnetic member352, while the magnet having the opposite charge would be used to attract themagnetic member352. Other alternatives known in the art for attracting and repelling amagnetic member352 can also be utilized.
• Various types of check valves are suitable for use with the[0103]pump320 to control the flow of fluid, gas, or other substance in the desired direction. In one embodiment, as shown in FIG. 3d,check valves348 and350 are passive flaps etched or molded in thesubstrate346. As shown in FIG. 3d,check valves348,350 are a substantially straight flap having a length that is longer than the width ofchannels342,344. The flap is angularly positioned across the width of the channel, with the end that is closer to the start of the flow being anchored to a sidewall of thechannels342,344, while the other end of the flap is free-floating. This type of construction can be achieved by cutting or etching around the substrate material to leave it attached to one sidewall, while cutting or etching through the material to free it from the other sidewall. If an injection molding process is used, the mold is continuous between the sidewall and the flap to leave it attached to the sidewall, while a space is left between the other end of the flap and the sidewall.
• The force of a substance, such as a fluid or gas, being pumped through[0104]channels342,344 tries to align the flap with the direction of the flow. The substance passes throughchannel342 as the free-floating end of the flap moves away from the sidewall with the direction of the flow caused by the vacuum that is created whendiaphragm338 is raised. The vacuum created by upward movement ofdiaphragm338 also forces the free end ofcheck valve350 into the sidewall ofchannel344, thereby preventing backflow fromchannel344. The reverse happens when the diaphragm moves downward and the fluid is propelled in one direction.
• It is anticipated that some embodiments of[0105]biosensor device102 would include one or more bi-directional valves. Further, the operation of both unidirectional and bi-directional valves could be controlled by the force of the flow created by actuatingdiaphragm338, or electronically using logic in valve controller164 (FIG. 1a) to open andclose valves348,350, in FIG. 3d.
• It is important to note that one or more channels, such as[0106]channel342 in FIG. 3d, can feed intopump chamber340. Likewise, one or more channels, such aschannel344, can be used to transport a substance out ofpump chamber340.
• FIG. 3[0107]fshows a diagram of a typical piezoelectric micropump380 found in the art that is suitable for use with the present invention in addition to, or instead of, pump320 (FIG. 3e). Pump380 includes apump chamber382 which is capped by heat-resistant glass layer388 which also forms the diaphragm.Piezoelectric element390 is bonded todiaphragm388. Applying a voltage fromvoltage source386 to thepiezoelectric element390 induces either an upward or downward deflection depending upon the polarity of the applied voltage. This changes the volume of thepump chamber382, causing it to draw fluid through an inlet valve, and to pump fluid through an outlet valve, on opposite strokes of the cycle. Applying a periodic excitation voltage causes diaphragm388 to oscillate, producing a pumping action. The flow rate is thus directly controlled by the frequency of the electrical drive signal to thepiezoelectric element390.
• [0108]Substrate392 can be fabricated from polymer or silicon material. The glass layer384 is bonded ontosubstrate392 using a suitable bonding method, such as anodic or epoxy bonding, to prevent leakage. Polyimides and thermal laminants can also be used for bonding and have the advantage of a lower bonding temperature.
• One way to mix very small amounts of two or more substances in[0109]microfluidic system104 is to feed the flow streams into one channel as they are directed to a reservoir or pump chamber. An alternative way includes injecting one substance into another using micro-nozzles. Referring now to FIG. 3g, one embodiment of mixer394 with micro-nozzles is shown that is suitable for use with the present inventionmicrofluidic system104. Mixer394 includes a mixingchamber396 with nozzles398 on one side. During operation, the mixingchamber396 is filled with one or more substances, and another substance is injected through the nozzles398, thereby generating a plurality of micro-plumes. The plumes effectively mix the substances without requiring any additional processing. Mixing time depends on injection flow rate, size of nozzles, distance between each nozzle and size of the mixing chamber. Nozzles with orifices as small as one (1) micrometer can be provided using known fabrication processes.
• Information from[0110]biosensor device102 can be accessed by authorized users whenbiosensor device102 is connected to an information network. One embodiment of components and connections between components ininformation network410 that can be used with the present invention is shown in FIG. 4. Users access information and interface withinformation network410 throughworkstations412.Workstations412 execute application programs for presenting information from, and entering data and selections as input to interface withinformation network410.Workstations412 also execute one or more application programs to establish a connection withserver416 throughnetwork420. Various communication links can be utilized, such as a dial-up wired connection with a modem, a direct link such as a T1, ISDN, or cable line, a wireless connection through a cellular or satellite network, or a local data transport system such as Ethernet or token ring over a local area network. Accordingly,network420 includes networking equipment that is suitable to support the communication link being utilized.
• Those skilled in the art will appreciate that[0111]workstations412 can be one of a variety of stationary and/or portable devices that are capable of receiving input from a user and transmitting data to the user. The devices can include visual display, audio output, tactile input capability, and/or audio input/output capability. Such devices can include, for example,biosensor system100, desktop, notebook, laptop, and palmtop devices, television set-top boxes and interactive or web-enabled televisions, telephones, and other stationary or portable devices that include information processing, storage, and networking components. Additionally, eachworkstation412 can be one of many workstations connected toinformation network410 as well as to other types of networks such as a local area network (LAN), a wide area network (WAN), or other information network.
• [0112]Server416 is implemented on one or more computer systems, as are known in the art and commercially available. Such computer systems can provide load balancing, task management, and backup capacity in the event of failure of one or more computer systems inserver416, to improve the availability ofserver416.Server416 can also be implemented on a distributed network of storage and processor units, as known in the art, wherein the modules and databases associated with the present invention reside onworkstations412, thereby eliminating the need forserver416.
• [0113]Server416 includesdatabase422 and system processes424.Database422 can reside withinserver416, or it can reside on another server system that is accessible toserver416.Database422 contains information regarding users as well as results from tests performed usingbiosensor device102. Consequently, to protect the confidentiality of such information, a security system can be implemented that prevents unauthorized users from gaining access todatabase422. Users can be authorized to transmit and/or receive information fromdatabase422. User interface114 (FIG. 1) can allow the user to download and/or retrieve results from one or more tests todatabase422.
• System processes[0114]424 include program instructions for performing analysis of data frombiosensor device102 and other information provided by the user. The type of analysis performed is based on the type of data being analyzed, and the type of information to be provided to the user.
• One application of[0115]biosensor system100 is generating and sharing information for medical diagnosis. A user can introduce a sample to be analyzed, such as a drop of blood or other bodily fluid, intomicrofluidic system104. As discussed above, a variety of different configurations can be implemented onmicrofluidic system104, depending on the specific test to be performed. Accordingly,microfluidic system104 includes the components, and the type and amount of reagents required to perform one or more assays on the sample.
• [0116]Biosensor system100 can screen for known pathogens for infectious diseases and/or markers for genetic disorders. After the sample is analyzed, the presence of a pathogen or a disease marker (gene/protein) above a specific level can be indicated. Data from each assay can be transmitted toserver416 directly frombiosensor system100 or viaworkstation412. The data is stored inserver416 using a personal, secured account that is generated for each user. A subscriber, such as a physician and/or other authorized individual, can be granted remote access to the user's account viainformation network420.
• Advantageously, the[0117]electromagnetic pumps100 do not require electrical interconnects to operate.
• Another advantage is that microfluidic system[0118]400 may be used to perform a variety of microfluidic and bio-analytical functions, and can have varying levels of complexity depending on the number of components included, and the functions to be performed.
• The foregoing detailed description has set forth various embodiments of the present invention via the use of block diagrams, flowcharts, and examples. It will be understood by those within the art that each block diagram component, flowchart step, and operations and/or components illustrated by the use of examples can be implemented, individually and/or collectively, by a wide range of hardware, software, firmware, or any combination thereof.[0119]
• The above description is intended to be illustrative of the invention and should not be taken to be limiting. Other embodiments within the scope of the present invention are possible. Those skilled in the art will readily implement the steps necessary to provide the structures and the methods disclosed herein, and will understand that the process parameters and sequence of steps are given by way of example only and can be varied to achieve the desired structure as well as modifications that are within the scope of the invention. Variations and modifications of the embodiments disclosed herein can be made based on the description set forth herein, without departing from the spirit and scope of the invention as set forth in the following claims.[0120]

Claims (42)

What is claimed is:

1. A microfluidic pump comprising:

a substrate including a chamber;

at least one channel in communication with the chamber;

a flexible diaphragm forming a wall of the chamber; and

a magnetic member attached to the diaphragm.

2. The pump ofclaim 1 further comprising:

a check valve positioned in the channel.

3. The pump ofclaim 2 wherein the check valve is unidirectional.

4. The pump ofclaim 2 wherein the check valve includes a flap having one end movably attached to one sidewall of the channel.

5. The pump ofclaim 1 further comprising an electromagnet positioned to attract and repel the magnetic member.

6. The pump ofclaim 5 further comprising:

a current source coupled to supply electric current to the electromagnet.

7. The pump ofclaim 6 further comprising:

a control system coupled to adjust the current output by the current source.

8. The pump ofclaim 1 further comprising a protective layer covering the top of the diaphragm.

9. The pump ofclaim 1 further comprising a protective layer covering the bottom of the substrate.

10. The pump ofclaim 5 wherein the electromagnet is positioned adjacent the magnetic member.

11. The pump ofclaim 5 wherein the electromagnet is positioned separate from the magnetic member.

12. A microfluidic pump comprising:

a substrate including a pump chamber;

at least one channel in communication with the pump chamber;

a flexible diaphragm overlying the pump chamber; and

means for actuating the flexible diaphragm.

13. The pump ofclaim 12 wherein the means for actuating the flexible diaphragm includes an electromagnet.

14. The pump ofclaim 12 wherein the means for actuating the flexible diaphragm includes a permanent magnet.

15. The pump ofclaim 13 further comprising:

a current source coupled to supply electric current to the electromagnet.

16. The pump ofclaim 15 further comprising:

a control system coupled to adjust the current output by the current source.

17. The pump ofclaim 12 further comprising:

a check valve positioned in the channel.

18. The pump ofclaim 12 wherein the substrate is a polymer material.

19. The pump ofclaim 12 wherein the substrate is injection molded.

20. The pump ofclaim 12 wherein the channel and the pump chamber are embossed in the substrate.

21. A system for transporting a substance, the system comprising:

a substrate including a pump chamber;

at least one channel in communication with the pump chamber;

a flexible diaphragm forming a wall of the pump chamber;

means for actuating the flexible diaphragm; and

a control system coupled to control the means for actuating the flexible diaphragm.

22. The system ofclaim 21 wherein the means for actuating the flexible diaphragm includes an electromagnet.

23. The system ofclaim 21 wherein the means for actuating the flexible diaphragm includes a permanent magnet.

24. The system ofclaim 22 further comprising:

a current source coupled to supply electric current to the electromagnet.

25. The system ofclaim 21 further comprising:

a check valve positioned in the at least one channel.

26. The system ofclaim 21 wherein the substrate is a polymer material.

27. The system ofclaim 21 wherein the substrate is injection molded.

28. The system ofclaim 21 wherein the channel and the pump chamber are embossed in the substrate.

29. A method for transporting a substance using a pump system, wherein the pump system includes a chamber, at least one channel in communication with the chamber, a flexible diaphragm forming a wall of the chamber, and a magnetic member attached to the diaphragm, the method comprising:

attracting the magnetic member to cause the substance to flow into the chamber; and

repelling the magnetic member to cause the substance in the chamber to flow out of the chamber.

30. The method ofclaim 29, wherein the pump system further includes a check valve positioned in the channel, the method further comprising:

opening the check valve while attracting the magnetic member; and

closing the check valve while repelling the magnetic member.

31. The method ofclaim 30 wherein the check valve is unidirectional.

32. The method ofclaim 30 wherein the check valve includes a flap having one end movably attached to one sidewall of the channel.

33. The method ofclaim 29, wherein the pump system further includes an electromagnet positioned to attract and repel the magnetic member, the method further comprising:

adjusting current supplied to the electromagnet to control attracting and repelling the magnetic member.

34. A method of fabricating a pump system for transporting a substance, the method comprising:

forming a pump chamber in a substrate;

positioning at least one channel in communication with the pump chamber;

forming at least a portion of a wall of the pump chamber with a flexible diaphragm; and

attaching a magnetic member on the flexible diaphragm.

35. The method ofclaim 34 further comprising:

positioning a magnet to attract and repel the magnetic member.

36. The method ofclaim 34, wherein the magnet is an electromagnet, the method further comprising

coupling a control system to control current to the electromagnet.

37. The method ofclaim 34 further comprising:

positioning a check valve in the at least one channel.

38. The method ofclaim 34 further comprising:

using a polymer material for the substrate.

39. The method ofclaim 34 further comprising:

injection molding the substrate.

40. The method ofclaim 34 further comprising:

embossing the pump chamber in the substrate.

41. The method ofclaim 34 further comprising:

positioning a protective layer over the pump system.

42. The pump ofclaim 34 further comprising:

positioning a protective layer under the pump system.

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